The development of muscle morphology, the regeneration of that morphology following injury and the manner in which muscle tissue ages are most likely controlled by the connective tissue components of muscle as opposed to the muscle cells themselves. To test this suggestion and to ascertain the functional importance of the extracellular matrix in this morphogenetic and morphosenectic phenomenon, we propose to isolate and chemically characterize the proteoglycans synthesized by muscle and muscle-related connective tissue components. Because proteoglycan is the single most influential molecular component responsible for hydration structuring characteristics of the extracellular environment, we believe that the characterization of these macromolecules will help us better understand this aspect of extracellular matrix physiology and its impact on muscle development, maturation and, as a long term and eventual goal, aging. This approach is built on our extensive experience in characterizing cartilage proteoglycans, on preliminary experiments conducted on developing muscle systems in culture and on an extensive literature which details the cellular and molecular biology related to muscle. When sufficient information concerning the structure and developmental biosynthesis from this in vitro system is available and models for these proteoglycans generated, experiments which characterize the proteoglycans from in vivo preparations from embryonic to adult will be conducted. Eventually, the experience gained with chick material from both the culture system and in vivo measurements will have to be used in explorations of muscle extracellular matrix in other animals, especially as related to aging, since the chicken may not be the optimal animal to use for specimens related to senescence. The prediction from our analysis of cartilage proteoglycans is that muscle proteoglycans will be synthesized in programmatically changing pattern with age. The long range goal is to attempt to delineate the mechanism(s) controlling this proteoglycan biosynthesis.